Electrostatic chucks and a particle deposition apparatus therefor

ABSTRACT

The present invention is directed to electrostatic chucks, methods for their use, the electrostatic deposition of objects, such as particles in a dry powder, onto recipient substrates, and the recipient substrates themselves that have been subjected to electrostatic deposition. In one aspect, the present invention provides an electrostatic chuck for electrostatically attracting an object or objects wherein the object is used in chemical or pharmaceutical assaying or manufacturing. The objects can be pharmaceutical substrates, for example, such as a pharmaceutical tablet. Additional embodiments of the invention provide chucks and their use to electrostatically attract particles, such as a pharmaceutically active ingredient, to a substrate, such as a tablet. In one aspect, the electrostatic chuck comprises a floating electrode, and is used to selectively attract particles to a substrate above the floating electrode, thereby providing for charge imaging for the deposition of particles in a selected image. Additionally, the invention provides comprising a sensing electrode, optionally for use with an electrostatic chuck, for sensing the number of particles attracted to the objects on the chuck or other substrate, thereby providing for deposition of an accurate amount of particles. Furthermore, the present invention provides objects having selected areas in which particles are applied to the object via electrostatic means.

The present application is a divisional of U.S. application Ser. No.08/661,210, filed Jun. 10, 1996, now U.S. Pat. No. 5,858,099, which is adivisional of prior U.S. application Ser. No. 08/630,050, filed Apr. 9,1996, now U.S. Pat. No. 5,846,595.

Related co-pending U.S. patent applications, “Inhaler Apparatus withModified Surfaces for Enhanced Release of Dry Powders,” filed Jun. 10,1996, now U.S. Pat. No. 5,871,010, “Inhaler Apparatus with an ElectronicMeans for Enhanced Release of Dry Powders,” filed Jun. 10, 1996, nowU.S. Pat. No. 5,857,456, Ser. No. 08/630,049(“Acoustic Dispenser,” filedApr. 9, 1996), now abandoned, and its continuation-in-part filed Jun.10, 1996, Ser. No. 08/630,012 (“Chucks and Methods for PositioningMultiple Objects on a Substrate,” filed April 9, 1996), now U.S. Pat.No. 5,788,814, Ser. No. 08/471,889 (“Methods and Apparatus forElectronically Depositing a Medicament Powder Upon Predefined Regions ofa Substrate,” filed Jun. 6, 1995, now U.S. Pat. No. 5,714,007, andcontinuation-in-part thereof filed Jun. 6, 1996, Ser. No. 08/467,647(“Apparatus for Electrostatically Depositing and Retaining MaterialsUpon a Substrate,” filed Jun. 6, 1995), now 5,669,973 and Ser. No.08/506,703 (“Inhaler Apparatus Using a Tribo-Electric ChargingTechnique,” filed Jul. 25, 1995), now U.S. Pat. No. 5,642,727, describe,inter alia, the electrostatic deposition of objects, such as particlesof powder, on a substrate.

The present invention is directed to electrostatic chucks, methods fortheir use including the electrostatic deposition of particles on anobjects, and the objects themselves that have been subjected toelectrostatic deposition. In one aspect, the present invention providesan electrostatic chuck for electrostatically attracting an object orobjects wherein the object is used in chemical or pharmaceuticalassaying or manufacturing. The objects can be pharmaceutical substrates,for example, such as a pharmaceutical tablet or an inhaler substrate.

Additional embodiments of the invention provide chucks and their use toelectrostatically attract particles, such as a pharmaceutically activeingredient, to a substrate, such as a tablet. In one aspect, theelectrostatic chuck comprises a floating electrode, and is used toselectively attract particles to a substrate above the floatingelectrode, thereby providing for charge imaging for the deposition ofparticles in a selected image. Additionally, the invention provides anelectrostatic chuck comprising a sensing electrode for sensing thenumber of particles attracted to the chuck, thereby providing fordeposition of an accurate amount of particles. Furthermore, the presentinvention provides objects having selected areas in which particles areapplied to the object via electrostatic means.

In the pharmaceutical industry, pharmaceutical compositions with anactive ingredient are prepared by mechanically mixing the activeingredient with pharmaceutically acceptable carriers. A major drawbackto this method is the inaccuracy of distribution of the activeingredient in the individual tablets of a batch. This problem isparticularly evident when the active ingredient is present in a lowdosage, and the inaccuracy of mechanical mixing can result in individualtablets in a single batch having different dosages.

Additionally, for example, some pharmaceutical compositions contain amixture of various carriers together with the active ingredient in whichthe carrier is not fully compatible with the active ingredient. Forexample, the active ingredient may be poorly soluble in the carrier orthe carrier may negatively affect the bioavailability of the activeingredient.

These drawbacks of the prior art are addressed by the present invention,in which electrostatic chucks are provided together with their use inthe pharmaceutical or chemical industries, providing for accuratedeposition of an active ingredient on a tablet, among other advantages.

SUMMARY OF THE INVENTION

The disadvantages heretofore associated with the prior art are overcomeby inventive technique and apparatus for holding an object or multipleobjects, such as tablets, without the use of mechanical force, fordeposition of a pharmaceutically active ingredient, for example. Thepresent invention provides advantages including cost-effectiveness,efficiency, and, for example, greater accuracy in the application of aspecified pharmaceutical dosage to a pharmaceutical substrate such as atablet. Further, the deposition of a pharmaceutically active ingredientusing static electricity is particularly useful, for example, when theactive ingredient is immiscible or otherwise incompatible with theremainder of the tablet or other substrate.

In one aspect, the present invention provides an electrostatic chuckcomprising a conductive layer having at least one electrode forelectrostatically attracting an object wherein the object is used inchemical or pharmaceutical assaying or manufacturing. For example, theobject can be coated with a pharmaceutically active compound. Theobjects can be numerous types of substrates, including, for example,objects that are suitable for human consumption. The objects can bepharmaceutical substrates, such as an inhaler substrate, apharmaceutical tablet, capsule, caplet, suppository, dressing, bandageand a patch. In certain embodiments, the pharmaceutical substrate is notdielectric.

Certain embodiments provide the use of an electrostatic chuck toelectrostatically attract objects, such as particles, to a recipientsubstrate. “Particles” are defined herein as objects having a size lessthan about one millimeter in width or diameter. Thus, the electrostaticchucks of the invention can be used, for example, to attract particlesof a powder having a pharmaceutically active ingredient to a recipientpharmaceutical substrate, which substrate may be pharmaceutically inert.

Another aspect of the present invention provides the use of anelectrostatic chuck to attract an object wherein the thickness of theobject is preferably less than about 5 mm, and more preferably, lessthan about 3 mm.

In one embodiment of the invention, the electrostatic chuck has twoelectrodes in the upper conductive layer exposed to the objects, and thetwo electrodes are preferably interdigitated. In other embodiments, thechuck has a single electrode in the upper conductive layer. The chuckcan be used, for example, to hold an object against gravitationalforces, or, for example, to position multiple objects on a substrate.See, for example, U.S. Pat. No. 5,788,814.

Certain aspects of the invention provide an electrostatic chuckcomprising a floating electrode, wherein the chuck is used toselectively attract objects, such as particles, to a substrate above thefloating electrode, thereby providing for charge imaging for thedeposition of particles in a selected image. Additionally, the inventionprovides a sensing electrode for sensing the number of objects, such asparticles, that have been deposited onto a recipient substrate. Incertain preferred embodiments, a sensing electrode is located on anelectrostatic chuck. The sensing electrode provides for deposition of anaccurate amount of objects, such as particles. The particles depositedon the recipient substrate can include, for example, a pharmaceuticallyactive ingredient.

Furthermore, the present invention provides objects having selectedareas in which particles are applied to the object via electrostaticmeans.

Additionally, in one aspect, the present invention provides anelectrostatic chuck comprising an inhaler substrate, the substratecomprising a conductive layer having at least one electrode forelectrostatically attracting particles for inhalation. Preferably, theparticles comprise particles of a dry powder comprising apharmaceutically active ingredient.

The present invention additionally provides methods using anelectrostatic chuck. For example, the invention provides a method ofchemical or pharmaceutical manufacturing comprising:

(a) providing an electrostatic chuck; and

(b) electrostatically attracting an object to the chuck,

wherein the object is used in chemical or pharmaceutical manufacturing.In addition to a method of manufacturing, the present invention providesthe use of an electrostatic chuck to electrostatically attract an objectto a substrate wherein the object is a support for a chemical reactionused in a chemical assay or to manufacture chemicals or pharmaceuticals.

The invention also provides the use of an electrostatic chuck toelectrostatically attract one object or multiple objects to a substratewherein the thickness of the object is less than about 3 mm.Additionally, the invention provides for the use of an electrostaticchuck having a bias potential for attracting an object to a substrate,the bias potential being less than the breakdown potential of thematerials forming the chuck.

The methods of the present invention can be used with numerous objectsincluding an edible substrate, a pharmaceutical substrate, such as aninhaler substrate, a tablet, capsule, caplet, suppository, dressing,bandage and a patch, and optionally when the substrate is notdielectric. Additionally, the methods of the invention can be used withparticles that include a pharmaceutically active ingredient, and themethods of the invention include their use to coat an object, such as atablet, with a pharmaceutically active compound.

Further, the invention provides a method of attracting a selected numberof particles to a substrate, comprising:

(a) providing an electrostatic chuck with a sensing electrode;

(b) applying multiple electrostatically charged particles to the chuck;and

(c) sensing the number of particles attracted to the chuck. This methodcan be used, for example, with particles of a dry powder wherein themethod is used to determine the amount of powder deposited on asubstrate attracted to the chuck.

Another aspect of the invention provides a method of depositingparticles onto selected areas of a substrate, the method comprising theuse of an electrostatic chuck with floating electrodes in areas of thechuck that correspond to the selected areas of the substrate.Additionally, the invention provides a method of manufacturing apharmaceutical composition comprising (a) providing a pharmaceuticalsubstrate; and (b) electrostatically depositing particles on thesubstrate, the deposition preferably comprising the use of anelectrostatic chuck. Preferably, the electrostatic chuck comprises afloating electrode and the particles are substantially deposited on anarea of the substrate corresponding to the floating electrode, and theelectrostatic chuck preferably further comprises a sensing electrode fordetermining the amount of particles deposited on the substrate.

In another aspect, the present invention provides a method for producinga dosage form comprising: (a) providing an electrostatic chuck having anarea that is x- or y-addressable; (b) contacting the chuck with objectscomprising a pharmaceutically active ingredient, wherein the objectssubstantially adhere to the chuck in the areas that are x- ory-addressable; and (c) releasing the objects onto a pharmaceuticalcarrier aligned with the areas of the chuck on which the objects areadhered. Preferably, the chuck has multiple areas that are x- ory-addressable, each area corresponding to a separate pharmaceuticalcarrier. Further, the objects are preferably substantiallysimultaneously deposited onto multiple pharmaceutical carriers. Thismethod can be used, for example, to form different dosage units, when atleast two of the pharmaceutical carriers receive a different number ofobjects. This method is particularly convenient for pharmaceuticallyactive ingredients such as hormones that are administered in varyingdosages, and it is desirable to form a pharmaceutical package containingmore than one type of dosage unit.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of a schematic representation of anelectrostatic chuck with interdigitated electrodes according to thepresent invention.

FIG. 2 is a top view of a schematic representation of the interdigitatedelectrodes of FIG. 6.

FIGS. 3A and 3B are circuit diagrams of an electrostatic chuck havingtwo electrodes, FIG. 3A depicting the chuck without a lower conductivelayer, and FIG. 3B depicting the chuck with a lower conductive layer.

FIG. 4A is a top view of a schematic representation of the singleelectrode of FIG. 9B.

FIG. 4B is a cross-sectional view of a schematic representation of anelectrostatic chuck with a single electrode on the upper conductivelayer, which protrudes from the dielectric layer, according to thepresent invention.

FIG. 4C is a cross-sectional view of a schematic representation of anelectrostatic chuck according to the present invention with a singleelectrode on the upper conductive layer, which is embossed in thedielectric layer.

FIG. 5 is a cross-sectional schematic view of an electrostatic chuckwith floating electrodes on the upper conductive layer for chargeimaging.

FIG. 6 is a top view of a floating electrode of FIG. 5.

FIG. 7 is a circuit diagram of an electrostatic chuck with a floatingelectrode on the upper conductive layer.

FIG. 8 is a schematic cross-sectional view of a sensing electrode.

FIG. 9 is a top schematic view of a sensing electrode, with the locationof the sensing electrode being outside the area of deposition.

FIG. 10A is a top schematic view of a sensing electrode, with thelocation of the sensing electrode being inside the area of deposition.

FIG. 10B is a top view of a schematic representation of a sensingelectrode, with the location of the sensing electrode in the shape of atablet, within the area of deposition.

FIG. 11 is a circuit diagram of an electrostatic chuck with a sensingelectrode.

FIG. 12A is a photograph of a top view of a floating electrode afterpowder deposition, in a chuck without the lower conductive layer, withthe printed circuit board attached. The photograph was taken at about50×magnification; therefore, the line adjacent to the photographrepresents a length of about 0.5 mm therein.

FIG. 12B is a photograph of a top view of a floating electrode afterpowder deposition, in a chuck with the lower conductive layer, with theprinted circuit board attached. The photograph was taken at about50×magnification; therefore, the line adjacent to the photographrepresents a length of about 0.5 mm therein.

FIG. 13A is a photograph of a top view of a floating electrode afterpowder deposition, in a chuck without the lower conductive layer, withthe printed circuit board removed. The photograph was taken at about50×magnification; therefore, the line adjacent to the photographrepresents a length of about 0.5 mm therein.

FIG. 13B is a photograph of a top view of a floating electrode afterpowder deposition, in a chuck with the lower conductive layer, with theprinted circuit board removed. The photograph was taken at about50×magnification; therefore, the line adjacent to the photographrepresents a length of about 0.5 mm therein.

FIGS. 14A-C are graphical representations of the detection of powderdeposited using a sensing electrode with an electrostatic chuck of thepresent invention. The x axis represents the time in minutes and the yaxis represents the charge in microcoulombs. dq/dt represents thedeposition rate.

FIG. 15 is a schematic diagram of an electrostatic chuck of the presentinvention for creating multi-dosage units.

FIGS. 16A-C provide three photographs of an electrostatic chuckaccording to the present invention. FIG. 16A shows the electrostaticchuck circuit; FIG. 16B shows a window mask for the chuck and FIG. 16Cshows the chuck assembly with an array of tablets.

FIG. 17A is a diagrammatic cross-section of a modified quartz crystalmonitor, and FIG. 17B is a circuit diagram of the monitor shown in FIG.17A.

FIG. 18 is a cross-sectional schematic view of an acoustic dispenseraccording to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

For purposes of this application, the following terms have the indicatedmeanings.

Acoustic dispenser: an apparatus for dispensing particles that employsvibration having a frequency in the acoustic (audible) range.

Chuck: a clamp for holding an object or objects.

Chuck for positioning objects: a chuck having a configuration that canbe used for substantially arranging objects on the chuck in a selectedpattern.

Electrostatic chuck: a clamp for holding an object or objects usingelectrostatic force.

Electrostatic chuck with conductive vias: an electrostatic chuck forpositioning objects, in which the chuck has a layer that determines thepositioning of the objects, and this layer has vias containing aconductive material.

Mechanical Chuck: a chuck that uses compression to hold an object.

Non-Mechanical Chuck: a chuck that does not use compression to hold anobject, including but not limited to a chuck that uses electrostatic orvacuum (i.e., negative pressure) means for such holding.

Object: a material thing.

Particle: an object equal to or less than about one millimeter in widthor diameter.

Pitch: the repeat distance between the edge of one well to thecorresponding edge of the adjacent well in, for example, a microtiterplate.

Recipient substrate: an object having a surface or layer that is coatedwith or will receive a coating of objects, such as particles.

Upper conductive layer: the conductive layer of an electrostatic chuckthat attracts or adheres objects to the chuck.

1. Uses of the Electrostatic Chucks of the Invention

“Chucks” are defined above as clamps for holding an object or objects.Instead of using conventional clamps that employ mechanical orcompressive force, the present invention is directed to the use ofstatic electricity in an electrostatic chuck as the means used by thecontext of the chuck to hold objects. The objects can optionally bepositioned, transported and deposited. Preferably, the chucks use aforce other than positive pressure for holding objects. The chucks ofthe present invention can be used, in one aspect, for positioningobjects, which is described in U.S. Pat. No. 5,788,814 (“Chucks andMethods for Positioning Multiple Objects on a Substrate,” filed Apr. 9,1996).

In one aspect, the present invention provides electrostatic chucks forelectrostatically attracting an object or multiple objects. Withoutbeing limited to any particular theory, it is believed that when anelectric potential is applied to the electrostatic chucks of theinvention, capacitors are formed between the electrodes of the chuck andobjects are held by the electrostatic force. One of the advantages ofusing an electrostatic chuck in the chemical or pharmaceutical industryis that, unlike plasma charging, electrostatic charging (also known astribocharging) generally does not negatively affect chemicals. Further,the use of an electrostatic chuck provides the ability to hold apharmaceutical substrate, for example, without requiring mechanicalforce that could disrupt the substrate.

The chucks of the present invention can be used to hold an object ormultiple objects against gravitational forces during chemical orpharmaceutical processing. Additionally, the present invention providesmethods of chemical manufacturing using a chuck to attract an object ormultiple objects to a substrate, the objects being used in chemicalmanufacturing. In another aspect, the present invention provides methodsof manufacturing a pharmaceutical composition by using a chuck toattract an object or multiple objects to a substrate, the objects beingused to manufacture the pharmaceutical composition. The chuck can bemanufactured to have an increased size in order to attract an objecthaving an increased surface area.

In one aspect, the present invention provides for the use of anelectrostatic chuck having a bias potential for attracting an object orobjects to a substrate. Preferably, the bias potential is greater thanabout 1000 volts. The use of the chuck according to the presentinvention provides for the possibility of a bias potential since a biaspotential does not necessarily cause damage to, for example, apharmaceutical substrate, unlike a wafer in the semiconductor industry,which is voltage sensitive.

When using an electrostatic chuck, preferably the temperature is betweenabout −50° C. to about 200° C., and preferably from about 22° C. toabout 60° C. The humidity is preferably between 0-100% wherein thehumidity does not cause condensation; more preferably, the humidity isabout 30%.

The use of the electrostatic chucks of the invention can be scaled upfor large scale continuous manufacturing, such as using a sheet of anedible substrate for use with tablets, for example, or a sheet of aninhaler substrate, which can be perforated, for example, into individualtapes for individual inhalers.

The present invention also provides methods for depositing a selectednumber of objects comprising: (a) providing an electrostatic chuckhaving an area that is x- or y-addressable; (b) contacting the chuckwith objects, wherein the objects substantially adhere to the chuck inthe areas that are x- or y-addressable; and (c) releasing the objectsonto a recipient substrate aligned with the areas of the chuck on whichthe objects are adhered. The present invention also provides methods forproducing a dosage form comprising: (a) providing an electrostatic chuckhaving an area that is x- or y-addressable; (b) contacting the chuckwith particles comprising a pharmaceutically active ingredient, whereinthe particles substantially adhere to the chuck in the areas that are x-or y-addressable; and //

(c) releasing the particles onto a pharmaceutical carrier aligned withthe areas of the chuck on which the particles are adhered. Advantages ofthe present invention include the ability to hold a pharmaceuticalsubstrate without the use of a mechanical means. Thus, for example, thepresent invention provides an electrostatic mechanism for holding atablet that is loosely compressed and that would crumble if held bymechanical means or by a vacuum chuck. Additionally, for example,without being held to a particular theory, it is believed that thepharmaceutically acceptable carriers, for example, in tablets arefrequently conductive and dissipate their charge within less than abouta millisecond. An electrostatic chuck provides an advantage bymaintaining its charge whereas a pharmaceutical substrate, for example,would otherwise lose its charge.

The present invention also provides electrostatic chucks that are usedto hold an object or multiple objects during processing in the chemicalor pharmaceutical industry. Such processing includes the deposition ofparticles on the objects, such as the deposition of a pharmaceuticallyactive powder on tablets. This is particularly useful, for example, whenthe active ingredient is incompatible with the remainder of the tablet.Furthermore, more than one type of ingredient, such as two activeingredients, can be coated on an object, such as a tablet. The tabletcan be further processed after the particles are deposited on it; forexample, the tablet can be coated after deposition.

Preferably, the particles are dispensed using an acoustic dispenser,described in U.S. Ser. No. 08/630,049.

Without being limited to a particular theory, the electric potentialgenerated by the electrostatic chucks of the present invention isbelieved to serve both for holding a conductive object in place, such asa tablet, and for attracting a charged object, such as particles withina powder, onto a recipient substrate. Additionally, the electrostaticchucks of the invention can be used for inhaler substrates. See, forexample, co-pending application entitled “Inhaler Apparatus with anElectronic Means for Enhanced Release of Dry Powders,” filedsimultaneously herewith. See also the section on charge imaging chucksbelow.

2. Objects Held by Electrostatic Chucks of the Invention

A. Sizes and Types of Objects

Preferably, the thickness of an object held by an electrostatic chuck ofthe present invention is less than about 300 mm, and more preferably,less than about 100 mm, even more preferably, less than about 50 mm,even more preferably, less than about 25 mm, even more preferably, lessthan about 10 mm, even more preferably, less than about 5 mm, and mostpreferably, less than about 3 mm. Thus, in certain preferredembodiments, the object is a small object, such as a particle equal toor less than about one millimeter in average width or diameter. Incertain preferred embodiments, the chucks of the invention are used withmultiple small objects, preferably having a size from about 5 microns toabout 500 microns, and preferably for use in the chemical orpharmaceutical industry. The use of an electrostatic chuck in thechemical and pharmaceutical industries is one of the novelties of thepresent invention.

In certain preferred embodiments, the objects held by a chuck arepharmaceutical substrates, and the objects are round, such as tablets.Alternatively, for example, the objects are oblong, and can be, forexample, capsules or caplets. When the object is a tablet, preferably ithas a thickness no greater than about 3 mm. The present inventionadditionally provides for the use of a chuck to hold an object orobjects which, in some embodiments, are coated with particles whilebeing held. In preferred embodiments, the particles are within a powdercomprising a pharmaceutically active compound.

Preferably, the powder is in dry micronized form, using for example, anair jet milling process, and the particles are at least about 1 micronin diameter, and preferably from about 1 to about 10 microns, and morepreferably about 4 to about 8 microns in diameter. Preferably, thepowder is electrostatically charged before application to the chuck, forexample, through admixture with beads such as by mechanical shaking.

Additional pharmaceutical substrates include, for example, asuppository, or an edible substrate such as a pharmaceutical tablet,capsule or caplet or a water soluble film such as a hydroxypropyl methylcellulose resin. Other substrates include dressings, bandages andpatches, as well as, for example, a substrate for an inhaler. Forexample, the inhaler can be a flat, ceramic disk upon which a pluralityof medicament dosages are positioned. See, for example, U.S. Pat. No.5,714,007.

The chucks of the present invention can be used for numerous other typesof objects, including but not limited to a thin conductive substratesuch as an edible polymeric substrate, which can be used as a substratefor deposition of a pharmaceutically active powder, and the substratecan subsequently be used, for example, to create or coat a tablet.Preferably, excess objects that are not electrostatically adhered to thechuck are removed before transferring the objects to a substrate. Torelease the objects, the application of voltage can be stopped, or forgreater force of removal, the voltage can be reversed.

In addition to pharmaceutical objects or particles, the electrostaticchucks of the present invention can be used to attract any otherparticle that can be adhered to an electrostatic chuck. Additionally,for example, the chucks can be used to attract and deposit liposomesinto capsules for cosmetics.

B. Composition of the Objects Held by the Chucks

Preferably, the tablets to be held by the electrostatic chucks of theinvention include a substantial amount of cellulose, preferably greaterthan about 50% cellulose, more preferably greater than about 60%cellulose, even more preferably greater than about 75% cellulose, evenmore preferably greater than about 90% cellulose, and most preferablyabout 95% cellulose. In other embodiments, the tablets include about 65%lactose and about 34% cellulose. In certain embodiments, the tabletsinclude about 80% lactose. Preferably, the tablets do not have aningredient which would cause them to deviate from being either a goodconductor or a good dielectric. For example, with a conductive tabletsuch as one that is substantially made of cellulose, preferably thetablet does not include dielectric metal oxides such as ferrous orferric oxide or titanium oxide. Preferably the amount of iron oxide, ifpresent, is less than about 1%. Additionally, the tablet preferably doesnot include moisture and preferably does not include a substantialamount of a salt such as sodium bicarbonate that becomes conductive withhigh humidity, thereby making the most efficient operation of theelectrostatic chuck affected by humidity.

The tablets may optionally have additional components, including but notlimited to sodium starch glycolate and magnesium stearate.

When an edible substrate, having for example, a pharmaceutically activepowder deposited onto it, is fused with a tablet, preferably the ediblesubstrate is made of substantially the same component as the tablet,such as cellulose. For example, hydroxypropyl methyl cellulose can beused, such as Edisol M Film M-900 or EM 1100 available from PolymerFilms Inc. (Rockville, Conn.).

Preferably, the density of the tablet is such that if it has a diameterof about 5.6 mm, the tablet weighs no more than about 100 mg. If thediameter of the tablet is twice as large, the weight can be proportionalto the square of the diameter.

The conductivity of a tablet can be determined by measuring the DCimpedance, by placing the tablet in an electrical circuit between avoltage source and a picoammeter. The capacitance of the tablet can bemeasured by placing the tablet sample in parallel with a Hewlett Packard4192A Low Frequency Impedance Analyzer set for 1 kHz. The tablets arepreferably painted on both sides with a thin layer of conductive silverpaint to ensure good electrical contact. Several formulations weretested, and conductivities between 2.4×10⁹Ω and 6.3×10⁹Ω were found. Therange of impedance was about 2×10⁹Ω to 23×10¹⁰Ω. The capacitance wasdetermined to be 0.3 pF to 0.5 pF, which correspond to a chargeretention time of 100 μsec. to 1 msec.

3. Charging of Objects

In certain preferred embodiments, the objects to be applied to the chuckare charged prior to their application. The charge can be, for example,either a plasma charge or an electrostatic charge, depending upon thenature of the object to be applied to the chuck. For instance, whenusing beads, either a plasma or electrostatic charge can be used sinceneither causes damage to the bead. For other objects that may be damagedby plasma charging, electrostatic charging is preferably used. Inpreferred embodiments, the methods include electrostatically chargingthe object before applying it to the chuck. For details regarding theuse of carrier beads for charging, see the continuation-in-part, filedsimultaneously herewith, of U.S. Ser. No. 08/630,049, filed Apr. 9, 1996now abandoned.

4. Configuration of the Chucks

The size of the chuck depends upon the number and size of objects to beattracted using the chuck. For example, a 2 inch by 2 inch chuck canhold about 100 tablets in which each tablet has a diameter of about 5.6mm. Preferably, the chuck is reusable and can be washed between uses.

When using a chuck of the present invention to hold a recipientsubstrate, such as a tablet, during deposition of particles, such as apowder containing a pharmaceutically active ingredient, the tablets arepreferably closely packed on the chuck so that only the tablets receivethe powder, and the chuck itself is not coated with powder. For example,the electrostatic chucks of the invention can be used to hold abouteighty-one tablets in a row of nine tablets by a column of nine tablets.

In one aspect, the present invention provides an electrostatic chuckcomprising a conductive layer forming at least one electrode forelectrostatically attracting multiple objects. In other preferredembodiments, the chuck comprises a conductive layer forming twoelectrodes, which, in certain embodiments, are serpentine orinterdigitated and provide for a higher probability that the area of thetwo electrodes covered by the same object are the same, thereforeobjects at different locations of the chuck are held at the samepotential. Additionally, the surface area is beneficially inverselyproportional to the object to be held by the chuck. For example, inpreferred embodiments, the electrode has a larger surface area toelectrostatically hold a smaller object. The conductive layer thatattracts or adheres objects to the chuck is termed an “upper conductivelayer”, and this layer is not necessarily the outermost layer of thechuck. For example, the upper conductive layer can have a thindielectric layer on top of it, between the conductive layer and theobjects. Further, the chuck may have more than one conductive layerforming an electrode, although only the conductive layer that attractsor adheres objects to the chuck is termed an “upper conductive layer”.

In certain preferred embodiments, the electrostatic chucks are made ofsolid state materials such as glass or silicon dioxide or other ceramicswhich impart good dielectric strength and therefore better attraction ofobjects. The better dielectric strength also provides for a thinnerlayer, and a lower voltage which increases safety. Further, thematerials are well-characterized, durable, mechanically strong andreadily available.

A. Electrostatic Chuck with Two Electrodes in the Upper Conductive Layer

Referring to FIG. 1, the lower conductive layer 610 of the chuck 620 iscoated with a dielectric layer 630. On top of the dielectric layer is anupper conductive layer 640 forming an interdigitated electrode, with afirst electrode 650 and a second electrode 660. A second dielectriclayer 670 is placed on top of the upper conductive layer 640. FIG. 2shows a top view of the two interdigitated electrodes 650 and 660. Thischuck 620 can be used to attract an object 680, as shown.

During use of an electrostatic chuck having an upper conductive layerwith two interdigitated electrodes, a voltage is applied across the twoelectrodes of the chuck, preferably about 200 to about 2000 volts. See,for example, Example 4 below. The voltage applied to an electrostaticchuck can be direct current voltage (DC) or alternative current voltage(AC) provided that the same amount of voltage is applied.

B. Mathematical Calculation of the Holding Force of the Chuck

Without being limited to a particular theory, assuming a 1 mm contactarea for the tablet, $\begin{matrix}{{Capacitance} = \quad {\frac{\varepsilon_{0}\varepsilon_{r}A}{d} = \frac{8.89 \times 10^{- 10} \times 1 \times 1 \times 10^{- 6}}{50 \times 10^{- 6}}}} \\{\approx \quad {17\quad {pF}}}\end{matrix}$ $E = {\frac{1}{2}C\quad V^{2}}$ $\begin{matrix}{F = \quad {\frac{\varepsilon}{X} = \frac{\varepsilon_{0}\varepsilon_{r}A\quad V^{2}}{2X^{2}}}} \\{\cong \quad \frac{17 \times 10^{- 12} \times (500)^{2}}{2 \times 5^{- 0} \times 10^{- 6}}} \\{= \quad {42.5\quad {µN}}}\end{matrix}$

For the capacitor, assuming that X=the thickness of dielectric layer,for a 60 mg tablet, the gravitational force=60×10⁻⁶ kg×9.8 N/kg{tildeover (=)}600 μN and the electrostatic force is therefore about 60 timesstronger than the force of gravity.

Without being limited to any particular theory, it is believed that theobject need not necessarily have direct physical contact with anelectrode in the upper conductive layer in order to be electrostaticallyheld by the chuck. When using the chuck having an upper conductive layerwith interdigitated electrodes to deposit a charged powder onto atablet, for example, the electrostatic force holding the tabletincreases as the charged powder is deposited on the tablet, therebyproviding an additional advantage in a stronger holding force. There isa limited amount of charged powder that can be deposited using theinterdigitated chuck, which is based on bias potential. Therefore, thischuck provides the advantage of the ability to determine the amount ofpowder deposited upon a substrate by measuring the amount of chargeremaining. The charge can be measured using, for example, anelectrometer or a picoammeter. The value of the charge can be used todetermine the mass of the powder deposited. The design of this chuckprovides for its ability to electrostatically hold virtually any objectthat is conductive relative to the strong dielectric layer on top of thechuck.

Without being limited to a particular theory, the following mathematicalformulas can be used to evaluate the holding force of the electrostaticchuck illustrated in the circuit diagram shown in FIG. 3. FIG. 3Arepresents a circuit diagram of an electrostatic chuck with an upperconductive layer having two electrodes, each electrode having an objectattracted to it, and in which the lower conductive layer is absent. FIG.3B represents a circuit diagram of a chuck with an upper conductivelayer having two electrodes, each electrode having the same objectattracted to it, and in which the lower conductive layer is present. Cp₁is the capacitance of the capacitor formed between an object, such as atablet, and the first electrode; CP₂ is the capacitance of the capacitorformed between an object, such as a tablet, and the second electrode; Rpis the resistance due to the object; and V represents the holdingpotential which is related to the force holding the object onto thechuck. Referring to FIG. 3B, Ce₁ is the capacitance of the capacitorformed between the lower conductive layer and the first electrode; Ce₂is the capacitance of the capacitor formed between the lower conductivelayer and the first electrode; and V_(f) represents the bias potential.

A conductive object and the electrode in the upper conductive layer forma capacitor with a capacitance approximately equal to $\begin{matrix}{C = \frac{\varepsilon_{0}\varepsilon_{r}A}{d}} & (1)\end{matrix}$

where ε₀, is the dielectric constant of a vacuum, and ε_(r) is therelative dielectric constant of the dielectric layer on top of theelectrodes in the upper conductive layer; A is the contact area and d isthe thickness of the dielectric layer. The force holding of theconductive object and the electrode in the upper conductive layer isgiven by: $\begin{matrix}{F = \frac{\varepsilon_{0}\varepsilon_{r}A\quad V^{2}}{2d^{2}}} & (2)\end{matrix}$

where V is the voltage across the dielectric layer. Assuming ε_(r)=3 fora polymer, V=350 V, d=10 μm and A=15 mm², the electrostatic force is0.24 N. If the material has a mass of 60 mg, the gravitational force is0.59 mN. The electrostatic force is over 400 times stronger than thegravitational force.

In the circuit diagram shown in FIG. 3, V_(ad)=V. Provided enoughcharging time elapsed after the voltage V is applied, V_(bc)=0. Whencharged powders land on R_(p), the voltage across the two capacitors isrearranged. However, the power supply maintains the overall voltage dropV_(ad) as a constant. In a practical design, C_(p1) is approximately thesame as C_(p2) and V_(ab)˜V_(cd)˜V/2. The overall attractive force isproportional to (V_(ab) ²+V_(cd) ²)˜V²/2. If the voltage on point b (orc) is altered due to the landing of the charge powders by V′, the newattractive force is proportional to V²/2+2V′²=V²/4+V′². As a result ofthe addition of the charged powder, the attractive force increases.Also, normal leakage current through the two capacitors of limitedresistance is supplied by the power supply as well.

The applied potential V can be maintained at a separated voltagedifference V_(f) with respect to ground. The potential at the conductivematerial (in this application, the conductive material is a tablet) isV_(f)+V/2. If the tablet is exposed to a cloud of charged powders, thepowders will experience the field due to the potential V_(f)+V/2 and beattracted or repelled according to the sign of the charge on powder. Ifthe resultant force is attractive, the powder will be deposited onto thetablet. Since both V_(f) and V can be controlled in magnitude as well asthe sign, the resultant force can be controlled so that it is attractivefor deposition.

Without being limited to any particular theory, it is believed thatbefore any conductive material is attached to the chuck shown in FIG. 1and in the circuit diagram in FIG. 3, the charges will be concentratedon the edges of the electrodes. There is a relatively weak fringingelectric field on the top of the electrostatic chuck. This field may notbe strong enough to cause charge redistribution in the tablet forattaching the tablet to the chuck. This limitation is removed by theaddition of a lower conductive layer beneath the chuck, also known as abackplane. This conductive layer causes the charges on the electrodes toredistribute more evenly across the electrodes. As a result, a higherfringing electric field on the top of the chuck and a better initialattraction between the tablet and the chuck are formed. The newequivalent circuit is shown in FIG. 3B.

C. Electrostatic Chuck with a Single Electrode in the Upper ConductiveLayer

In other preferred embodiments, the chuck comprises an upper conductivelayer having a single electrode. Preferably, the chuck includes threelayers. The bottom layer is preferably a lower conductive layer made ofmetal, for example, such as aluminum. Alternatively, for example, thebottom layer can be semiconductive, such as a silicon wafer. The middlelayer is a dielectric layer preferably having a high dielectricstrength, such as thermally grown silicon dioxide. The top layer is anupper conductive layer forming the electrode, which can extend from thetop of the dielectric layer externally, or can be embossed whereby itextends internally into the dielectric layer. The upper conductive layeris made of a conductive material, such as a metal, for example, copperwires, or a semiconductor, for example, polycrystalline silicon.Preferably, the upper conductive layer has no significantly negativeeffect on a pharmaceutically active compound. In preferred embodiments,the thickness of the upper conductive layer is from about 100 nm toabout 500 nm. Preferably, the upper conductive layer comprisesconductive stripes, and when used to attract multiple objects, the widthof the area between the stripes preferably is approximately equal to theaverage diameter of the objects, thereby providing for complete coverageof the electrode when the maximum number of objects are held by thechuck. Thus, when the chuck is used to hold objects while particles arebeing deposited on the objects, this configuration provides forsubstantially eliminating the deposition onto the chuck itself. See, forexample, FIG. 16.

Referring to FIG. 4B, for example, the electrostatic chuck 910 has alower conductive layer 920, with a dielectric layer 930 on top of it.The upper conductive layer 940 either protrudes outward from thedielectric layer 930, as shown in FIG. 4B, or is embossed into thedielectric layer 930, as shown in FIG. 4C. A top view of the striationsin the upper conductive layer 940 is shown in FIG. 4A. During use of theelectrostatic chuck 910, a bias potential is applied between the upperconductive layer 940 and the lower conductive layer 920.

Without being limited to a particular theory, it is believed that whenthe above-described chuck with a single electrode in the upperconductive layer is used, for example, to electrostatically hold tabletswhile a charged powder is applied to the tablets, there is no chargeredistribution in the tablet, but rather, the tablet is directly chargedby contact with the electrode. Therefore, an unlimited amount of chargedpowder can be deposited on the tablets.

5. X-Y-Addressability of the Chucks and Their Uses

One of the conductive layers, such as the lower conductive layer of theelectrostatic chuck, can be made x-addressable or x-y-addressable suchthat the location of the objects attracted to the chuck can be selected.For example, in an x-addressable chuck, the lower conductive layer hasrows in which a single row can be activated at one time. Thus, one canselect the placement of objects only on a specific row of theelectrostatic chuck, rather than on every row or of the chuck. In anx-y-addressable chuck, the area of the lower conductive layercorresponding each row and column, and therefore, preferably to eachobject, can be made independent of the remainder of the lower conductivelayer corresponding to any of the other rows and columns. Thus, forexample, one can select the placement of objects only on specific areasof the electrostatic chuck, rather than throughout the chuck.

Further, the present invention provides an electrostatic chuckcomprising a configuration for depositing a selected number of objectsonto a recipient substrate. Preferably, the objects are less than about3 mm in thickness, and the configuration of the chuck preferablycomprises a conductive layer having an x or y-addressable area fordepositing a selected number of objects onto the recipient substrate.Preferably, the chuck has multiple areas that are x- or y-addressable,each area preferably corresponding to a separate substrate such as apharmaceutical carrier. In preferred embodiments, the objects aredeposited substantially simultaneously onto multiple substrates, and incertain embodiments, the substrates are connected. For example, thesubstrates can be a pharmaceutical carrier and the objects can be, forexample, particles in a powder, microspheres or liposomes which containa pharmaceutically active ingredient, and together they create apharmaceutical dosage form. When the substrates are connected, amultidosage pack can be formed in which the dosage decreases, forexample, from one unit to the next, such as with a multidosage pack forbirth control. The dosage can be determined by the number of objectsplaced into each pharmaceutical carrier using an electrostatic chuck.Thus, the present invention provides a multidosage form having units inwhich each unit has a dosage, at least two units having differentdosages, the dosages being determined by the number of microspheres inthe unit. In certain preferred embodiments, the average diameter of themicrospheres is from about 1 to about 500 microns, in some instances,preferably about 100 to 500 microns, and in other instances, preferablyabout 50 microns.

Preferably, the microspheres comprise a pharmaceutically acceptablepolyalkylene, such as polyethylene glycol, which is preferably at aconcentration of at least about 90%, and more preferably, about 95%polyethylene glycol. The chucks described herein such as for attractingtablets, for example, and for creating charge images, with anotherdielectric layer, can be used for creating the above describedmultidosage forms. See, for example, FIG. 15.

6. Charge Imaging Electrostatic Chucks with Floating Electrodes

In further preferred embodiments, electrostatic chucks of the inventionare provided for use in charge imaging. Specifically, such anelectrostatic chuck comprises a floating electrode for charge imaging.An electrostatic chuck for charge imaging comprises three layers,preferably with an optional fourth layer. The bottom layer is the lowerconductive layer, which is also known as the backing electrode. Thesecond layer, on top of the lower conductive layer, is a dielectriclayer. The third layer is an upper conductive layer on top of thedielectric layer, and this upper conductive layer has two types ofelectrodes, floating electrodes and shielding electrodes. In preferredembodiments, the floating electrodes are electrically isolated from theother conductors, and there is a gap between the floating and shieldingelectrodes. The fourth (optional) layer, on top of the upper conductivelayer, is a dielectric layer, which is preferably the layer havingcontact with the medicament powder. Without being limited to aparticular theory, it is believed that when a potential is appliedacross the shielding and backing electrodes, a charge redistributionoccurs on the floating electrodes. This charge redistribution causeselectrostatically charged objects to be attracted to the areas of thechuck corresponding to the floating electrodes, thus resulting indeposition in these areas. Preferably, there is a high fringing field inthe gap between the floating and shielding electrodes, but this field ispreferably not large enough to cause electrical discharge.

The lower conductive layer can be made, for example, of metal, such assilver, copper or aluminized polypropylene, and is preferably about 500nm in thickness. The dielectric layer can be made of, for example,polyimide, polypropylene, or a semiconductive layer, such as a ceramic,for example, SiO₂, such as a thermally grown silicon dioxide, and ispreferably about 0.5 to about 2 mils thick. The upper conductive layeris preferably made of a metal, such as silver. Preferably, the upperconductive layer is made of a material that does not negatively affectpharmaceutically active materials.

The upper conductive layer can be made of, for example, a thin gold filmcoating, and preferably, the floating and shielding electrodes have thesame thickness, which is preferably about 500 nm. In preferredembodiments, the gap between the floating electrode and the shieldingelectrode is from about 25 microns to about 500 microns. The shape ofthe floating electrode can be varied, and can be irregular, so long asthe gap between the floating electrode and the shielding electroderemains substantially constant. In certain preferred embodiments, thefloating electrode is round, and forms a dot that can be used to createa selected pattern. In certain preferred embodiments, the shieldingelectrode is grounded. The shielding electrode is biased with respect tothe lower conductive layer. The polarity of the bias is preferablyopposite of the powder to be deposited on the substrate.

The fourth layer, on top of the upper conductive layer, is an optionalthin dielectric layer, which is preferably made of polyimide or anothermaterial of high dielectric strength, and preferably has a thickness ofabout 10 microns to about 50 microns.

The floating electrodes of the charge imaging chuck determine thepattern of deposition of the medicament powder on the substrate, andhold the powder thereon. During the deposition of powder, the chargeimaging chuck is electrically connected to a power source, which issubsequently disconnected after deposition. The floating electrodes canbe configured, for example, to spatially determine individual dosages ona substrate. Such substrates include, for example, a tablet and aninhaler substrate.

In preferred embodiments for charge imaging, the floating electrodes areused to selectively attract particles to a substrate in contact with thefloating electrodes. Preferably, the substrate has physical contact withthe floating electrodes. Without being limited to a particular theory,it is believed that the use of floating electrodes on the electrostaticchuck generates an image of charges by capacitive coupling. Eachfloating electrode has a charge which is shifted as charged particlescontact the electrode. The process of deposition of charged particles onthe floating electrode continues until the floating electrode can nolonger shift potential, at the point in which it has the same potentialas the shielding electrode.

Referring to FIG. 5, for example, the chuck 1110 has a lower conductivelayer 1120, with a dielectric layer 1130 on top of it. The dielectriclayer has an upper conductive layer 1140 on top of it. The upperconductive layer 1140 is electrically connected, but with a gap 1150between a shielding electrode 1160 and a floating electrode 1170. A topview of the upper conductive layer 1140 is shown in FIG. 6, with thefloating electrode 1170 in the center, and a gap 1150 between thefloating electrode and the surrounding shielding electrode 1160. Thearea of the lower conductive layer 1120 corresponding to each floatingelectrode can be made addressable in rows, like the x-addressablechucking system described above, or individually addressable, like thex-y-addressable chucking system described above.

During use, a bias potential is applied between the shielding electrodeand the lower conductive layer. If the particles to be deposited arepositively charged, the bias potential will be negative, and if theparticles to be deposited are negatively charged, the bias potentialwill be positive. Preferably, the shielding electrode is connected toground. During deposition of particles, the length of time of thedeposition will preferably be continued until each and every floatingelectrode has reached its limit in which the potential of the floatingelectrode matches the potential of the shielding electrode.

Using an electrostatic chuck with floating electrodes to deposit powderonto a substrate, the amount of powder deposited on the substrate isdetermined by the charge or bias potential of the chuck, and only afinite amount of powder can be deposited. Without being limited to aparticular theory, it is believed that the deposition of powder endswhen the charges on the floating electrode can no longer beredistributed, which occurs when the shielding electrode and thefloating electrode have substantially the same potential. Preferably,both the floating and shielding electrodes will be at ground potentialwhen the deposition is complete. The amount of powder to be depositedcan therefore be controlled by controlling the bias potential, and it isunrelated to the duration of deposition, once the limit has beenreached. Furthermore, the pattern of deposition is determined by thepattern of the floating electrodes, which creates a charge image.

For example, a chuck can be used for charge imaging on a substrate todetermine the deposition of particles in a particular pattern on thesubstrate. In preferred embodiments, particles of a powder having apharmaceutically active ingredient are deposited in a selected patternonto a recipient pharmaceutical substrate. In certain preferredembodiments, the recipient substrate is a thin dielectric material, suchas polypropylene or another thin edible substrate such as hydroxypropylmethyl cellulose, preferably having a thickness of about 25 microns.

Alternatively, for example, an electrostatic charge imaging chuck with afloating electrode can be used to form an inhaler substrate, and todetermine the electrostatic deposition of dry powder, for example, ontothe substrate. The charge imaging chuck can be used, for example, todetermine the spatial location of individual dosages on a substrate.Additionally, the conductive layer of the electrostatic chuck in theinhaler substrate can be used for electronically assisted release of thepowder, as described in co-pending application entitled “InhalerApparatus with an Electronic Means for Enhanced Release of Dry Powders,”filed simultaneously herewith.

Further, the charge imaging chuck can be used outside the pharmaceuticalindustry, such as for the determination of the deposition pattern of acandy coating on a food item. The electrostatic charge imaging chucks ofthe invention can be used to hold objects, for example, for theapplication of a design, such as a candy coating on an edible substrate.Alternatively, for example, the electrostatic charge imaging chucks canbe used to hold objects for the application of a dry powder paint.

Without being limited to a particular theory, the following mathematicalformulas can be used to evaluate the amount of powder that can be heldby the electrostatic chuck having a floating electrode, which isillustrated in the circuit diagram provided in FIG. 7. Referring to FIG.7, C is the capacitance of the capacitor formed between the lowerconductive layer e_(l) and the floating electrode e_(f). Cs is the straycapacitance of the capacitor formed between the floating electrode e_(f)and the lower conductive layer e_(l). C′ is the capacitance of thecapacitor formed between the floating electrode e_(f) and the virtualelectrode e_(v), which is formed by the deposited charged powders. Thepotential of the floating electrode e_(f) can only be some value betweenthose of the shielding electrode e_(s) and the lower conductive layere_(l), the shielding electrode e_(s) being grounded in the circuitdiagram shown in FIG. 7.

The maximum charge that the floating electrode can hold depends on thebias potential and the capacitor C according to the equation Q_(max)=CV.If the fringing field is ignored in order to calculate the maximumcharge, the following equation applies:$Q_{\max} = {{C\quad V} = {\frac{\varepsilon_{0}\varepsilon_{r}A}{d}\quad V}}$

where A is the surface area of the floating electrode and d is thethickness of the dielectric layer between the floating electrode and theshielding electrode.

Because C_(s) is very small compared to C, the deposited charge Q′ isapproximately equal to Q. The mass M of the deposited powder will be asfollows:$M = {\frac{Q_{\max -}}{\mu} \cong {\frac{\varepsilon_{0}\varepsilon_{r}A}{d}\quad \frac{m}{q}\quad V}}$

where μ is the charge over mass ratio of the charged powder. By way ofexample, if ε_(r)=2, d=50 μm, the diameter of floating electrode=4 mm,μ=50 μC/g, and V=8 kV, M will be 1.2 mg. Thus, the maximum mass ofpowder expected to be deposited under these conditions will be 1.2 mg.

Since C_(s)<<C, Q′=C′V′≈Q.

Therefore, the maximum amount of changed powder is provided by thefollowing equation:$\frac{Q^{\prime}}{\mu} \approx {\frac{\varepsilon_{0}\varepsilon_{r}A}{d}\quad \frac{m}{q}\quad V}$

In addition to providing electrostatic chucks, the present inventionalso provides methods of charge imaging or depositing particles ontoselected areas of a substrate, the method including the use of anelectrostatic chuck with floating electrodes in areas of the chuck thatcorrespond to the selected areas of the substrate. Further, the presentinvention also provides for an object having selected areas in whichparticles are applied to the object via electrostatic means. Inpreferred embodiments, the particles comprise a pharmaceutically activeingredient. Preferably, the object is suitable for human consumption. Incertain embodiments, the object comprises a pharmaceutical substratesuch as an inhaler substrate, a tablet, suppository, dressing, bandageor a patch. Preferably, the amount of particles applied to the objectare predetermined using a sensing electrode in the electrostatic chuck.

Advantages of the use of an electrostatic chuck for deposition ofparticles and for charge imaging include the ability to coat a substratein a more accurate and more uniform manner, which is particularlyimportant when the dosage of active ingredient is low, such as fromabout 1 μg to about 1 mg. Other low dosage ranges include for example,from about 1 μg to about 500 μg, and from about 10 μg to about 250 μg,and from about 20 μg to about 100 μg, such as about 25 μg. Further, theuse of an electrostatic chuck for deposition of particles and for chargeimaging provides the advantage, for example, of a mechanism for applyingan active ingredient to a pharmaceutical carrier that may be immiscibleor otherwise incompatible with the active ingredient.

7. Sensing Electrode for Determining the Amount of Objects Deposited ona Recipient Substrate

In addition to providing electrostatic chucks with floating electrodesfor charge imaging, the present invention provides chucks with sensingelectrodes to sense the amount of charge deposited on a substrate.Furthermore, a single chuck can have both floating and sensingelectrodes. In certain aspects of the present invention, the amount ofcharge that can be deposited on the chuck is limited to a finite number,and this limitation provides a mechanism for accurately determining theamount of powder deposited on the substrate held by the chuck.

In another aspect, the present invention provides an electrostatic chuckhaving a sensing electrode for sensing the number of particles attractedto the chuck, particularly when the chuck is not self-limiting withrespect to the amount of charged particles that can be deposited onto asubstrate held by the chuck. The electrostatic chucks, or other surfacesupon which a recipient substrate is located, optionally include sensingelectrodes to sense the amount of charge deposited on the recipientsubstrate. In certain aspects of the present invention, the amount ofcharge that can be deposited, for example, on an electrostatic chuck islimited to a finite number, and this limitation provides a mechanism foraccurately determining the amount of powder deposited on the substrateheld by the chuck. Alternatively, the amount of deposition may not beself-limiting. A sensing electrode can be used with an acousticdispenser, for example, to determine the amount of powder deposited ontoa tablet, wherein the powder includes a pharmaceutically activeingredient. Thus, the sensing electrode provides a more accurate anduniform way of dispensing a selected amount of objects. For example, theinvention provides for the accurate deposition of a selected amount of apharmaceutically active ingredient deposited on a substrate, especiallywhen the active ingredient is present in small doses.

The sensing electrode preferably has two layers. The bottom layer is alower conductive layer forming an electrode made of a metal, forexample, such as aluminum. The top layer, which is exposed to theparticles being deposited, is a dielectric layer, and is made of amaterial having a high dielectric strength, such as aluminum oxide.Additionally, for example, the sensing electrode can be made of a thinaluminized polypropylene sheet or a thin polyimide sheet with a copperbacking. Without being limited to a particular theory, it is believedthat the charged particles land on the dielectric layer and induce anequal and opposite charge on the conductive layer. Due to the presenceof the dielectric layer, the possibility of charge neutralization issignificantly lowered.

Referring to FIG. 8, for example, the sensing electrode 1310 isconstructed of a lower conductive layer 1320 and an upper dielectriclayer 1330. As shown in FIG. 9, the sensing electrode 1310 can beplaced, for example, in an area outside the substrate 1410 receiving thedeposition of particles. In this figure, the sensing electrode 1310 isin the shape of a ring, and other shapes can also be used. The sensingelectrode 1310 can also be placed, for example, within the area of thesubstrate 1410 receiving the deposition of particles as shown in FIG.10A, when there is a single substrate 1410 receiving deposition.Alternatively, for example, when there are multiple substrates 1410, thesensing electrode 1310 can be placed within the area of deposition,preferably in the shape of one of the substrates 1410 receivingdeposition, such as a tablet. Referring to FIG. 10B, for example, theshape of the sensing electrode 1310 mimics the shape of one of thesubstrates 1410.

The sensing electrode is preferably located in an area that provides foran amount of particles to be deposited on the sensing electrode indirect relation to the amount of deposition on the substrate. More thanone sensing electrode can be used with a single substrate. For example,the presence of two sensing electrodes with deposition on a singlesubstrate can be used to determine the relationship between the amountof deposition occurring on the substrate and in areas outside thesubstrate. The mass of the particles deposited onto the substrate(s) isdetermined once the charge of the sensing electrode is measured.

To measure the amount of charge deposited, the sensing electrode isconnected in series with a capacitor of known value. For example, a 1 nFcapacitor will induce 1 volt when 1 nC of charge is collected. The otherpole of the known capacitor is attached to ground, and the potentialacross the capacitor is measured. A circuit diagram to illustrate theset-up is shown in FIG. 11. Referring to FIG. 11, V_(m) is a highimpedance voltmeter or an electrometer, C is the capacitance of acapacitor of known value, such as 1 μF, C′ is the capacitance of thecapacitor formed between the sensing electrode e_(s) and the depositedcharge e_(p) resulting from the deposition of charged particles.

Without being limited to a particular theory, the following mathematicalformulas can be used to evaluate the measurement of deposited charges bythe sensing electrode according to the above circuit diagram.

C′ is the capacitor formed by the sensing electrode and the chargedparticles. C is a capacitor of known value. C has a zero initial charge.When charged particles land on the sensing electrode, they cause anequal amount of opposite charge to be induced on the electrode whichwill subsequently induce an equal amount of opposite charge on C. Theoverall effect results in an equal amount and equal sign of chargeinduced on C, which can be measured by an electrometer. Furthermore, thedominating electrical noise associated with an active power source isremoved. The collected charge Q′ is equal to C times V.

With this monitoring method using the sensing electrode, two parametersneed to be predetermined to monitor the amount of actual deposition.These two parameters are the q/m (charge to mass) ratio of the chargedpowder and the relation factor k between the monitored charge Q′ and thedeposited charge Q on the deposition area of interest (i.e. k=Q/Q′).Hence, the deposited mass M is determined by the equation:$M = \frac{Q^{\prime}}{k\quad \frac{q}{m}}$

The reliability of the sensing electrode requires that the variable k issubstantially constant throughout the deposition.

The use of a sensing electrode is preferred over the use of an ammeteror voltmeter within the circuit since the sensing electrode provides theadvantages, for example, of correcting for collection of charges fromthe ambient atmosphere and other leakage paths induced by the chuck.

Preferably, the charge:mass ratio of the objects to be dispensed ismeasured during the deposition process to provide feedback control fortermination of deposition when the desired number of objects have beendeposited. For example, feedback control can be used to monitordeposition of a pharmaceutical powder until the appropriate dosage hasbeen achieved.

The average charge:mass ratio can be measured, for example, using avelocimeter and a modified quartz crystal monitor. Referring to FIG.17A, the quartz crystal monitor 1305 has a top sensing layer 1307 and abottom layer 1309 for connection to a meter. The quartz crystal monitoris modified by adding a charge sensing layer 1308, which is a secondconductive layer, and a dielectric layer 1312, as illustrated in FIG.17A. This modification causes the monitor to sense both charge and massat the same time. See, for example, the circuit diagram of the monitorshown in FIG. 17B, in which Cs is the capacitor due to the dielectriclayer, which measures the collected charge.

Preferably, at least two charge:mass monitors are used, one with theacoustic dispenser, and the other with the chuck or other means holdingthe recipient substrate or substrates.

Thus, in another aspect, the present invention provides a method ofattracting a selected number of multiple particles to a substrate,comprising (a) providing an electrostatic chuck with a sensingelectrode; (b) applying multiple electrostatically charged particles tothe chuck; and (c) sensing the number of particles attracted to thechuck. Preferably, the particles are particles of a dry powder and themethod is used to determine the amount of powder deposited on asubstrate attracted to the chuck. The invention therefore provides amethod of accurately determining the dosage in a pharmaceutical tablet.

Additionally, the invention provides a method of manufacturing apharmaceutical composition comprising (a) providing a pharmaceuticalsubstrate; and (b) electrostatically depositing particles on thesubstrate, the deposition preferably comprising the use of anelectrostatic chuck. Preferably, the electrostatic chuck comprises afloating electrode and the particles are substantially deposited on anarea of the substrate corresponding to the floating electrode, and theelectrostatic chuck preferably further comprises a sensing electrode fordetermining the amount of particles deposited on the substrate.

8. Objects Created Using The Electrostatic Chucks of the Invention

The invention additionally provides objects having selected areas inwhich particles are applied to the object via electrostatic means, suchas charge imaging. The use of electrostatic means creates a moreaccurate deposition of particles in a selected image, thus providing fora manner of identification of such an object. The deposition also showsgreater uniformity, and provides for less waste of particles.

In preferred embodiments, the particles comprise a pharmaceuticallyactive ingredient, and the object is suitable for human consumption, andpreferably comprises a pharmaceutical substrate such as a tablet,capsule or caplet. In other preferred embodiments, the object is asuppository or it is selected from the group consisting of an inhalersubstrate, a dressing, bandage and a patch. Preferably, the amount ofparticles applied to the object are predetermined using a sensingelectrode in the electrostatic means. Additionally, in preferredembodiments, the particles are applied to the object using an acousticdispenser described below.

One embodiment of the acoustic dispensers of the invention is shown inFIG. 18. According to this figure, the acoustic dispenser 1710 has aspeaker 1720 within a container 1730. On top of the speaker 1720 is aconductive layer 1740. On top of this layer 1740 is a dielectric layer1750. On top of the dielectric layer 1750 is a membrane 1760, which iscomposed of a conductive layer and a dielectric layer, with thedielectric layer facing the outside and in contact with the particles(not shown) propelled by the membrane 1760.

Referring again to FIG. 18, above the vibration membrane 1760 foracoustic vibration is a separation membrane 1770, such as a mesh, forseparating out objects having more than one size. The separationmembrane 1770 allows only smaller particles 1910, such as particles of apowder, to pass through, leaving larger particles 1920, such as carrierbeads, behind it. The separation membrane is preferably a #270 mesh(Newark Wire Cloth Co., Newark, N.J.) for particles from about 4 toabout 6 microns in diameter and preferably a #200 mesh (Newark WireCloth Co., Newark, N.J.) for particles greater than about 6 microns.

Referring once again to FIG. 18, the separation membrane 1770 isattached to a container 1780 for the objects (not shown), and thecontainer 1780 has a design that enhances acoustic vibration, as shown.Above the separation membrane 1770 is a substrate 1790, for receivingthe objects that are dispensed. The substrate 1790 can be, for example,a substrate attached or adhered to an electrostatic chuck.

The invention is further illustrated by the following non-limitingexamples.

EXAMPLE 1

Electrostatic Chuck with an Upper Conductive Layer Having TwoInterdigitated Electrodes

An electrostatic chuck with an upper conductive layer having twointerdigitated electrodes was fabricated as follows. A glass substratewas used, the substrate having an ITO (indium tin oxide) interdigitatedelectrode, forming an upper conductive layer less than about 25 micronsthick. On top of the upper conductive layer was a thin polystyrene layerusing Scotch brand tape, having about 1 mil thickness.

In one test, 1000 volts was applied across the electrodes and a tabletweighing about 65 mg and having a diameter of about 5.6 mm was held tothe chuck. When 1400 volts were applied, the tablet was repelled fromthe chuck, possibly due to a surge resulting in a discharge due to arepulsive force.

In a second test, a tablet was placed on top of the tape and 500 V D.C.was applied to the electrodes. The chuck was turned upside down and thetablet was held in place by the chuck.

In a third test, three tablets were applied to the chuck using 500 V andthe voltage was decreased until all three fell off the chuck. The firsttablet fell off at 300 V, the second tablet fell off at 200 V, and thethird tablet fell off at 100 V. The test results showed that the holdingforce is proportional to V².

In another test, six hundred volts was applied to one of the twointerdigitated electrodes of the chuck, and the other electrode wasgrounded. One tablet was placed on the polystyrene side of the chuck,and the tablet remained on the chuck after turning the chuck upside downand subjecting the tablet to the force of gravity.

The chuck was also tested for depositing powder on a tablet while heldby the chuck. Using air propulsion to deposit a positively chargedsteroid in a 3% suspension of beads, it was determined that at leastabout 47 μg was deposited.

EXAMPLE 2

Electrostatic Chuck with a Single Electrode in the Upper ConductiveLayer

An electrostatic chuck having a single electrode in the upper conductivelayer was configured as follows. The bottom of the chuck was a lowerconductive layer made of aluminum layered onto a dielectric layer madeof polyimide laminated onto copper (Good Fellows, Berwyn, Pa.). Thethickness of the polyimide layer was about 2 mils. Three copper wires ontop of the polyimide formed the upper conductive layer, and functionedas an electrode. The thickness of the copper layer was about 4 mils. Thedistance between the copper wires was about 5.6 mm. Eighty-six tabletswere used, each having a diameter of about 5.6 mm and each weighingabout 65 mg, and being made of about 95% cellulose and about 3% lactose,each with a thickness of about 2 mm. The tablets were adhered to thechuck for approximately five minutes, using 1500 volts applied betweenthe upper and lower conductive layers.

A steroid drug powder was applied to the tablets held by the chuckdescribed above as follows. A mixture of 3% drug with Kynar coated steelbeads (Vertex Image Products, Yukom, Pa.) having a diameter of about 100microns was stored in a Teflon bottle. 585.0 mg of drug powder, in acombination of drug and beads weighing 20.6354 g, was deposited on thetablets for about 6 minutes, using the acoustic dispenser described inExample 8 below at a frequency of 87 Hz, which was determined to be theoptimum frequency for the dispenser. The mesh of the acoustic dispenserfor separating drug powder from beads was placed at a distance of 0.5 to1.0 inches from the tablets receiving the powder.

EXAMPLE 3

Electrostatic Chuck with Floating Electrodes

An electrostatic chuck with floating electrodes having the followingconfiguration was tested. The lower conductive layer was made of coppertape and was about 4 mils in thickness. The next layer was a dielectriclayer made of Scotch brand polystyrene tape and about 1 mil inthickness. On top of the dielectric layer was an upper conductive layermade of a standard multipurpose through hole wire wrapped board(Radioshack) and about 0.0625 inch thick, forming an electrode, with agap between a shielding electrode and a floating electrode, which areelectrically connected. The floating electrode was round, and about 2.1mm in diameter. The shielding electrode was round, and about 2.5 mm indiameter. The gap between the shielding and the floating electrode wasabout 200 microns. A substrate was placed on the upper conductive layer,the substrate being a dielectric layer made of Scotch brand polystyrenetape and about 1 mil in thickness.

To use the chuck, about −1800 volts were applied to the upper conductivelayer. Next, steroid drug particles were applied to the chuck using thedispenser described in Example 8.

FIGS. 12-13 show the deposition of the powder on a floating electrodeusing a bias potential of −1800 volts with the chuck described above.The lower conductive layer, which is a printed circuit board, shows thecontrol of the alignment of the powder during deposition. In FIGS. 12Aand 13A, the lower conductive layer was omitted whereas in FIGS. 12B and14B, it was present. FIG. 12A shows that, in the absence of the lowerconductive layer, the charged particles accumulate at the edges of thefloating electrode. FIGS. 12B and 13B, in contrast, show that in thepresence of the lower conductive layer, the charged particles areuniformly spread throughout the floating electrode. The greatestquantity of powder deposited was found in the conditions present in FIG.13B, in the presence of the lower conductive layer.

EXAMPLE 4

Electrostatic Chuck with Sensing Electrode

An electrostatic chuck with a sensing electrode is constructed asfollows. The sensing electrode consists of a lower conductive layer madeof aluminum and having on top of it a dielectric layer made of aluminumoxide. A sensing electrode is placed on the electrostatic chuck so thatit is outside the recipient substrate that is subject to deposition. Thesensing electrode is used to indirectly determine the amount ofdeposition of charged particles by measuring the change in charge beforeand after deposition.

Another electrostatic chuck is constructed with a sensing electrodeplaced on the chuck in an area within the recipient substrate, therebycausing both the sensing electrode and the recipient substrate to besubject to deposition. In this case, the sensing electrode is used todirectly determine the amount of deposition of charged particles bymeasuring the change in charge before and after deposition.

A third electrostatic chuck is constructed with two sensing electrodes,one placed within the recipient substrate, and the other placed outsidethe recipient substrate. In this case, the sensing electrode within therecipient substrate is used to directly determine the amount ofdeposition of charged particles by measuring the change in charge beforeand after deposition, and is also used to calibrate the measurement ofdeposition by the sensing electrode outside the area of deposition.

A sensing electrode in a ring configuration was fabricated usinganodized aluminum oxide (aluminum as the conductive layer forming theelectrode and the oxide layer as the dielectric). 15 g of beads wereused and were shaken together with a micronized steroid drug powder(cortisone, Aldrich Chemical Co., Milwaukee Wis.) for about 30 minutes.Two concentrations of powder were used, one having 450 mg of powder per15 g beads (3% mixture) and one having 900 mg of powder for 15 g beads(6% mixture). 1800 volts were applied to the electrostatic chuck.Acoustic energy was used to propel the powder according to Example 8,using either 1400 (corresponding to about 12 Watts), 1600 or 1800. Thechange in charge during deposition was measured by recording the voltageon the electrometer every 30 seconds for the first two minutes and everyminute thereafter until 30 minutes total had passed. The amount ofpowder deposited on a pre-weighed amount of aluminum foil was alsomeasured.

Multiple tests were undertaken by performing deposition on aluminumfoil, the time for complete deposition taking about five minutes. Testsshowed that with steady state deposition, k varies up to 4% in eitherdirection. k is the ratio between the monitored charge Q′ and thedeposited charge Q and is actually a function of all operationalparameters of the chuck and acoustic dispenser; therefore, k isdetermined experimentally. A k inconsistency in excess of 10% isaccompanied by a change of dispenser characteristic. The data obtainedin tests of the sensing electrode is provided in Tables VI and VIIbelow, and FIGS. 14A-C, which provide a graphical representation of theexperimental data using a sensing electrode in the guard ringconfiguration.

TABLE VI Time Q Q′ Budio Time q q′ Time dq/dt dq′/dt Time q/q′ dq/dq′q/q′ analysis 0 0.00021 0.00115  900 0 0 0 5 0.000372 0.001102 50.337568 average after 0.58499 18 minutes 5 0.00207 0.00666 1600 50.00186 0.00551 5.5 0.01576 0.02488 5.5 0.337568 0.63341 Std deviation0.020353 5.5 0.00995 0.0191 1600 5.5 0.00974 0.01795 6 0.0138 0.01886 60.542618 0.731707 Relative 0.034792 deviation 6 0.01685 0.02853 1600 60.01664 0.02738 6.5 0.01546 0.02458 6.5 0.607443 0.628967 average after0.569577 7 minutes 6.5 0.02458 0.04082 1600 6.5 0.02437 0.03967 7 0.01560.02956 7 0.614318 0.52774 Std deviation 0.026827 7 0.03238 0.0556 16007 0.03217 0.05445 8 0.01429 0.02603 8 0.590817 0.548982 Relative 0.0471deviation 8 0.04667 0.08163 1600 8 0.04646 0.08048 9 0.01218 0.02307 90.5772865 0.527958 average after 0.561399 5 minutes 9 0.05885 0.10471600 9 0.05864 0.10335 10 0.00951 0.0173 10 0.566296 0.549711 Stddeviation 0.052168 10 0.06836 0.122 1600 10 0.06815 0.12085 11 0.008040.01675 11 0.563922 0.48 Relative 0.092925 deviation 11 0.0764 0.138751600 11 0.07619 0.1376 12 0.00768 0.0165 12 0.553706 0.465455 12 0.084080.15525 1600 12 0.08387 0.1541 13 0.0076 0.01725 13 0.544257 0.44058 130.09168 0.1725 1600 13 0.09147 0.17135 14 0.00804 0.0157 14 0.533820.512102 Average 25 over 25 minutes 14 0.09972 0.1882 1600 14 0.099510.18705 15 0.00841 0.0146 15 0.531997 0.576027 Deposition 1.0056 rate(mg/min) 15 0.10813 0.2028 1600 15 0.10792 0.20165 16 0.00845 0.0144 160.535185 0.586806 Dep. rate 0.580515 (μg/min/ mm 2) 16 0.11658 0.21721600 16 0.11637 0.21605 17 0.00946 0.0178 17 0.538625 0.531461 Dep. rate14.40048 (μg/min/ tablet) 17 0.12604 0.235 1600 17 0.12583 0.23385 180.01075 0.016 18 0.53808 0.671875 Time for 35 2.430474 μg (low dose) 180.13679 0.251 1600 18 0.13658 0.24985 19 0.01048 0.017 19 0.5466480.616471 Time for 250 17.36053 μg (high dose) 19 0.14727 0.268 1600 190.14706 0.26685 20 0.01216 0.0191 20 0.551096 0.636649 q/m (μC/g)11.79282 20 0.15943 0.2871 1600 20 0.15922 0.28595 21 0.01305 0.0189 210.556811 0.690476 21 0.17248 0.306 1600 21 0.17227 0.30485 22 0.01270.016 22 0.565098 0.79375 Average last 5 5 minutes 22 0.18518 0.322 160022 0.18497 0.32085 23 0.01293 0.0218 23 0.5765 0.593119 Deposition1.054461 rate (mg/ min) 23 0.19811 0.3438 1600 23 0.1979 0.34265 240.01179 0.0095 24 0.577557 1.241053 Dep. rate 0.608722 (μg/min/ mm 2) 240.2099 0.3533 1600 24 0.20969 0.35215 25 0.0113 0.0177 25 0.5954560.638418 Dep. rate 15.10019 (μg/min/ tablet) 25 0.2212 0.371 1600 250.22099 0.36985 26 0.0118 0.0153 26 0.597513 0.771242 Time for 352.317852 μg (low dose) 26 0.233 0.3863 1600 26 0.23279 0.38515 27 0.01070.019 27 0.604414 0.563158 Time for 250 16.55609 μg (high dose) 270.2437 0.4053 1600 27 0.24349 0.40415 28 0.0118 0.0197 28 0.6024740.598985 28 0.2555 0.425 1600 28 0.25529 0.42385 29 0.0125 0.0183 290.602312 0.68306 29 0.268 0.4433 1600 29 0.26779 0.44215 30 0.01190.0138 30 0.605654 0.862319 30 0.2799 0.4571 1600 30 0.27969 0.45595

TABLE VII dq/dq′ analysis average after 18 minutes 0.733839 Stddeviation 0.192065 Relative deviation 0.261727 average after 7 minutes0.629475 Std deviation 0.16644 Relative deviation 0.264411 average after5 minutes 0.633389 Std deviation 0.157774 Relative deviation 0.249094Foil mass before deposition 160.86 Foil mass after deposition 186 Massgain 25.14 Length (in) 1.79 Width (in) 1.5 Area (in 2) 2.685 Area (mm 2)1732.255 Tablet diameter (mm) 5.62 Tablet diameter (mm 2) 24.80639Capacitor value (μF) 1.06

We claim:
 1. A particle deposition apparatus comprising: (a) a chuck forsecuring a substrate on a surface of the chuck, the chuck comprising aconductive layer having therein at least one electrode configured andarranged to electrostatically attract charged particles to coat at leasta portion of a surface of the secured substrate, the electrostaticattraction resulting from a bias potential applied to the electrode; and(b) a charged particle dispenser having an outlet positioned andarranged for dispensing charged particles so that they adhere to thesecured substrate.
 2. The particle deposition apparatus of claim 1,wherein the chuck has a substantially planar surface.
 3. The particledeposition apparatus of claim 1, wherein the at least one electrode isat least two electrodes configured and arranged to attract particles tomultiple distinct portions of the secured substrate or multiple distinctsecured substrates.
 4. The particle deposition apparatus of claim 1,wherein the chuck comprises a vacuum chuck mechanism for securing thesubstrate.
 5. The particle deposition apparatus of claim 1, comprisingat least one floating electrode and at least one adjacent electrode nearto but insulated from the floating electrode, wherein a particleattracting voltage is induced in the floating electrode by a potentialapplied to the adjacent electrode.
 6. The particle deposition apparatusof claim 5 comprising a voltage source for applying a potential to theadjacent electrode to induce a particle-attracting field at the floatingelectrode.
 7. The particle deposition apparatus of claim 1, wherein thedispenser is adapted to dispense particles of 1 micron to 10 microndiameter.
 8. The particle deposition apparatus of claim 7, wherein thecharged particle dispenser further comprises a jet mill.
 9. The particledeposition apparatus of claim 1, wherein the chuck is adapted toelectrostatically attract charged particles to the secured substratewhen bias potentials of 200 V to 2,000 V are applied to the electrode.10. A particle deposition apparatus comprising: (a) a chuck adapted tosecure a film on a surface of the chuck, the chuck comprising aconductive layer having therein at least one electrode configured andarranged to electrostatically attract charged particles to coat at leasta portion of a surface of the secured film, the electrostatic attractionresulting from a bias potential applied to the electrode; and (b) acharged particle dispenser having an outlet positioned and arranged fordispensing charged particles so that they adhere to the securedsubstrate.
 11. The particle deposition apparatus of claim 10, whereinthe dispenser is adapted to dispense particles of 1 micron to 10 microndiameter.
 12. The particle deposition apparatus of claim 10, wherein thechuck is adapted to electrostatically attract charged particles to thesecured substrate when bias potentials of 200 V to 2,000 V are appliedto the electrode.
 13. The particle deposition apparatus of claim 10,wherein the chuck is adapted to secure a film with a thickness of lessthan 3 mm.
 14. A particle deposition apparatus comprising: (a) a chuckadapted to secure a film on a surface of the chuck, the chuck comprisinga conductive layer having therein at least two electrodes configured andarranged to electrostatically attract charged particles to coat at leasttwo discrete areas of a surface of the secured film, the electrostaticattraction resulting from a bias potential applied to at least one ofthe at least two electrodes; and (b) a charged particle dispenser havingan outlet positioned and arranged for dispensing charged particles sothat they adhere to the secured substrate.
 15. The particle depositionapparatus of claim 14, wherein the dispenser is adapted to dispenseparticles of 1 micron to 10 micron diameter.
 16. The particle depositionapparatus of claim 14, wherein the chuck is adapted to electrostaticallyattract charged particles to the secured substrate when bias potentialsof 200 V to 2,000 V are applied to at least one of the at least twoelectrodes.
 17. A particle deposition apparatus comprising: (a) a chuckadapted to secure one or more substrates on a surface of the chuck, thechuck comprising a conductive layer having therein at least twoelectrodes configured and arranged to electrostatically attract chargedparticles to coat at least two discrete areas of a surface of thesecured film, the chuck configured for x-y control such that the chuckcan be operated to selectively attract charged particles to a subset ofthe discrete areas, the electrostatic attraction resulting from a biaspotential applied to at least one of the at least two electrodes; and(b) a charged particle dispenser having an outlet positioned andarranged for dispensing charged particles so that they adhere to thesecured substrate.